Rejection of transplanted organs is the main barrier of transplantation today. It occurs as a result of humoral and cell-mediated responses by the recipient to specific antigens present in the donor tissue. These antigens are known as major histocompatibility complex (MHC) molecules. In humans, this group of molecules is referred to a human leukocyte antigen (HLA) complex molecules in humans.
Acute rejection usually occurs within the first weeks after transplantation. It is typically caused by mismatched HLA antigens that are present on all cells, which leads to activation of T cells in the host (or transplant recipient). HLA antigens are polymorphic therefore the chance of a perfect match is extremely rare. Endothelial cells in vascularized grafts such as kidneys are typically the earliest victims of acute rejection. Damage to the endothelial lining is often an early predictor of irreversible acute graft failure. The risk of acute rejection is highest in the first 3 months after transplantation, and is lowered by immunosuppressive agents in maintenance therapy.
The incidence of acute cellular rejection of renal allografts has decreased over the past decade (USRDS Annual Data Report, 2009). This has been attributed at least in part to the use of new immunosuppressive agents with higher potency on T-cell mediated responses. However, the incidence of acute rejection with evidence of vascular injury (i.e., transplant arteritis or capillaritis and/or C4d deposition) has not been positively impacted (USRDS Annual Data Report, 2009). In acute vascular rejection (AVR), cell-mediated, antibody-mediated and complement mediated pathways concur to vascular damage (Solez, K., et al., Am J Transplant, 2008. 8(4): p. 753-60). In most if not all forms of AVR of solid organ transplants, immune-mediated endothelial injury leading to a significant apoptotic response is a major characteristic (Solez, K., et al., supra; Shimizu, A., et al., Kidney Int, 2000. 58: p. 2546-58; Shimizu, A., et al., Lab Invest, 2002. 82(6): p. 673-86; Shimizu, A., et al., Kidney Int, 2002. 61: p. 1867-1879; Shimizu, A., et al., J Am Soc Nephrol, 2005. 16(9): p. 2732-45).
There is a need for the development of novel markers and methods for the prediction and/or diagnosis of acute vascular rejection, and/or for determining the risk of acute vascular rejection.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.